The proposed research seeks to learn more about hemostatic and fibrinolytic mechanisms through these approaches: 1) Observations on patients with congenital hemorrhagic diseases. In the hemophiliacs we have had a particular interest in frequent evidence of liver dysfunction and its relationship to treatment with factor concentrates. Liver biopsies have been done in about 20 individuals with abnormal liver function tests. Pathology has varied from chronic persistent hepatitis to chronic active hepatitis. 2) Observations on patients with acquired hemorrhagic or thrombotic disease. Over 340 patients with DIC and 100 with blocking inhibitors have been studied and data are being processed for publication. 3) Study of the phylogenetic development of coagulation mechanisms. The blood from many different animals from different vertebrate classes has been studied. Publications include studies on opossum, elephants, porpoise, monkeys, bats, hedgehogs, goats, echidna, elasmobranchs, and turkeys.